phase ii study of irinotecan liposomes in first-line treatment of metastatic colorectal cancer

Conditions: Metastatic Colorectal Cancer

Summary: to evaluate the objective response rate, disease control rate, progression-free survival, overall survival, surgical conversion rate and safety of irinotecan liposome combined with 5-fu/lv+ bevacizumab regimen in first-line treatment of advanced metastatic colorectal cancer patients.

this is a phase ii clinical study to evaluate the efficacy and safety of the combination regimen of irinotecan liposome injection in the first-line treatment of metastatic colorectal cancer. patients will receive liposomal injections of irinotecan 70mg/m\^2 d1, bevacizumab 5mg/kg d1, lv 400mg/m\^2 d1, 5-fu 400mg/m\^2, then 2400mg/m\^2, continuous intravenous infusion for 46-48h, d1-2. 86 eligible patients will be enrolled.

Eligibility criteria:
inclusion criteria: * 18\~85 years old. * histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma. * ras/braf v600e mutant or right half colon cancer is known. * pmmr/mss is known. * the unresectable stage of metastatic disease has not received any systemic antitumor therapy. * for subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 6 months removed from the date of last administration of neoadjuvant or adjuvant therapy. * ecog 0\~1, patients ≥75 years old need an ecog score of 0 * the presence of at least 1 measurable lesion that can be evaluated according to the recist v1.1 criteria. * normal bone marrow and organ function: ① neutrophils (anc) ≥1.5×10\^9/l, platelets (plt) ≥100×10\^9/l, hemoglobin (hb) ≥80g/l, albumin (alb) ≥30 g/l, white blood cells (wbc) ≥3.0×10\^9/l, and no bleeding tendency; ② ast, alt and alkaline phosphatase (alp) were all ≤2.5× upper limit of normal range (uln), and ≤5×uln when liver metastases occurred; the total bilirubin level doesn't exceed the upper limit of the agency's normal range; serum creatinine (cr) ≤1.5×uln or creatinine clearance ≥40 ml/min (calculated according to cockroft-gault) * understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form. exclusion criteria: * known or suspected central nervous system metastasis. * received irinotecan/irinotecan liposomes/bevacizumab before enrollment. * had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment. * previous treatment-related toxicity didn't return to nci-ctcae v5.0 i or below(except hair loss and peripheral neuropathy). * the use of cyp3a, cyp2c8, and ugt1a1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment. * severe gastrointestinal dysfunction, gastrointestinal perforation, intraperitoneal abscess, and fistula. * intestinal obstruction, signs and symptoms of intestinal obstruction, or the stent has been previously implanted and the stent has not been removed before the screening period. * interstitial lung disease. * tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding). * patients with fluid accumulation that couldn't reach a stable state but small amount of ascites on imaging without clinical symptoms could be enrolled. * any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc. * have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer. * patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding. * the researchers didn't consider it appropriate to participate in this study.